The goal of this proposal is to test the general hypothesis that due to the heavy burden of infectious disease and low energy balance, Tsimane forager-horticulturalists of the Bolivian Amazon experience more heart and kidney damage due to infection but less vascular disease and diabetes due to metabolic pathways than do people in developed nations. The Tsimane are Bolivian forager-horticulturalists that live with no electricity running water, or waste disposal, and have extremely limited access to modern medicine. To accomplish our goal, there are three specific aims of this competitive revision to the existing R01 The Human Life Course and the Biodemography of Aging. Aim 1 is to measure the prevalence and incidence of vascular, heart, kidney and diabetic disease among the Tsimane, a forager-horticultural society living in a pre-modern context. Aim 2 is to assess and test hypotheses regarding the relative importance of inflammation, infection and metabolic factors on the etiology of vascular, heart, diabetic, and kidney disease. Aim 3 is to analyze within and among community variation to assess the physical, behavioral and psychosocial impacts of lifestyle change and of social support on disease risk. The addition of this project will allow us to build a cross-sectional and longitudinal profile of a large sample of adults to model interactions between infection, diet, physical activity, psychosocial factors and organ functioning and damage in a population that reached maturity in a pre-modern, highly infectious environment. We will employ a combination of methods (serum and urine analysis, electrocardiogram, ultrasound of heart, kidney and carotid artery, and medical exams) to assess atherosclerosis, heart and kidney disease and diabetes. As the Tsimane are undergoing rapid change, we will also be able to assess within-population variance by examining the effects of acculturation on cardiovascular and renal disease at the community and individual level, as well as individual-level estimates of diet, physical activity and psychosocial factors. We will also compare our results to those obtained in the U.S. and other countries, to assess differences in how source of inflammation, whether infection, smoking or obesity, can impact the development of chronic disease, along with other factors, and how the nature of chronic disease itself can vary under different ecological regimes and lifestyles. PUBLIC HEALTH RELEVANCE: This renewal will provide detailed information on the nature of heart and kidney disease in a pre-modern population of forager-horticulturalists of South America experiencing similar demographic conditions as those in mid-19th century Europe. Investigation of arterial, heart, kidney and diabetic disease in a large sample of older adults can reveal unique insights about the relative contributions of diet, energy expenditure, infection and inflammation on the rate of physiological aging in a wide range of societies including the contemporary American experience. The results, combined with measures of aging and disease in other populations such as the U.S. and Indonesia, may help to explain the historical increases in life expectancy over the past several centuries.